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Proteolysis of Surfactant Protein D by Cystic Fibrosis Relevant Proteases

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Abstract

Surfactant protein D (SP-D) is an important innate host defense molecule that has been shown to interact with cystic fibrosis (CF)-associated pathogens. Previous studies demonstrated that rat SP-D is highly resistant to degradation by a wide range of proteolytic enzymes. The aim of this study was to examine whether human SP-D can be degraded by CF relevant proteases ex vivo and in vitro. Bronchoalveolar lavage fluids (BALFs) of 11 patients with CF in a stable clinical condition were examined for SP-D by immunoblotting. In vitro, purified human SP-D was treated with human leukocyte elastase, proteinase 3, cathepsin G or Pseudomonas elastase followed by immunoblotting with specific antibodies to SP-D. In BALF of 8 of the 11 patients investigated, proteolytic fragments or absence of SP-D were detected. In vitro proteolysis of SP-D was observed in a time-dependent manner for each protease applied. The presence of Ca++ at a physiologic concentration delayed, but did not prevent the degradation. We conclude that SP-D is an important target of numerous proteases present in the CF lung. Host defense is probably impaired due to proteolysis of SP-D and may contribute to the suppurative lung disease in CF.

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Acknowledgements

This project was supported by a grant from Mukoviszidose e.V. Bonn, Germany.

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Authors and Affiliations

  1. Lung Research Group, Children's Hospital of Ludwig Maximilians University, Munich, Germany

    C. von Bredow, A. Wiesener & M. Griese

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  1. C. von Bredow
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  2. A. Wiesener
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  3. M. Griese
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Correspondence to M. Griese.

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von Bredow, C., Wiesener, A. & Griese, M. Proteolysis of Surfactant Protein D by Cystic Fibrosis Relevant Proteases . Lung 181, 79–88 (2003). https://doi.org/10.1007/s00408-003-1008-z

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  • DOI: https://doi.org/10.1007/s00408-003-1008-z

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